Coarse-grained simulations of proton-dependent conformational changes in lactose permease

2016 ◽  
Vol 84 (8) ◽  
pp. 1067-1074 ◽  
Author(s):  
Yead Jewel ◽  
Prashanta Dutta ◽  
Jin Liu
Keyword(s):  
Conformational Changes ◽  
Coarse Grained ◽  
Lactose Permease ◽  
Coarse Grained Simulations

Coarse-grained simulation: a high-throughput computational approach to membrane proteins

2008 ◽  
Vol 36 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Mark S.P. Sansom ◽  
Kathryn A. Scott ◽  
Peter J. Bond
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayer ◽  
High Throughput ◽  
Protein Interactions ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Lactose Permease ◽  
Coarse Grained Simulations ◽  
Dynamics Simulations ◽  
Good Agreement

An understanding of the interactions of membrane proteins with a lipid bilayer environment is central to relating their structure to their function and stability. A high-throughput approach to prediction of membrane protein interactions with a lipid bilayer based on coarse-grained Molecular Dynamics simulations is described. This method has been used to develop a database of CG simulations (coarse-grained simulations) of membrane proteins (http://sbcb.bioch.ox.ac.uk/cgdb). Comparison of CG simulations and AT simulations (atomistic simulations) of lactose permease reveals good agreement between the two methods in terms of predicted lipid headgroup contacts. Both CG and AT simulations predict considerable local bilayer deformation by the voltage sensor domain of the potassium channel KvAP.

scholarly journals The P1 and P2 helices of the Guanidinium-II riboswitch interact in a ligand-dependent manner

2021 ◽  
Author(s):  
Christin Fuks ◽  
Sebastian Falkner ◽  
Nadine Schwierz ◽  
Martin Hengesbach
Keyword(s):  
Single Molecule ◽  
Conformational Changes ◽  
Environmental Conditions ◽  
Structural Information ◽  
Coarse Grained ◽  
Regulation Mechanism ◽  
Dependent Manner ◽  
Loop Formation ◽  
Coarse Grained Simulations ◽  
Kissing Loop

ABSTRACTRiboswitch RNAs regulate gene expression by conformational changes induced by environmental conditions and specific ligand binding. The guanidine-II riboswitch is proposed to bind the small molecule guanidinium and to subsequently form a kissing loop interaction between the P1 and P2 hairpins. While an interaction was shown for isolated hairpins in crystallization and EPR experiments, an intrastrand kissing loop formation has not been demonstrated. Here, we report the first evidence of this interaction in cis in a ligand and Mg2+ dependent manner. Using single-molecule FRET spectroscopy and detailed structural information from coarse-grained simulations, we observe and characterize three interconvertible states representing an open and kissing loop conformation as well as a novel Mg2+ dependent state for the guanidine-II riboswitch from E. coli. The results further substantiate the proposed switching mechanism and provide detailed insight into the regulation mechanism for the guanidine-II riboswitch class. Combining single molecule experiments and coarse-grained simulations therefore provides a promising perspective in resolving the conformational changes induced by environmental conditions and to yield molecular insights into RNA regulation.

scholarly journals Trapping On-Pathway Intermediates for Large Scale Conformational Changes with Coarse-Grained Simulations

2017 ◽  
Vol 112 (3) ◽  
pp. 485a
Author(s):  
Laura Orellana ◽  
Özge Yoluk ◽  
Oliver Carrillo ◽  
Modesto Orozco ◽  
Erik Lindahl
Keyword(s):  
Conformational Changes ◽  
Large Scale ◽  
Coarse Grained ◽  
Coarse Grained Simulations

Coarse-Grained Molecular Dynamics Simulations of Sugar Transport Across Lactose Permease

2015 ◽  
Author(s):  
Yead Jewel ◽  
Prashanta Dutta ◽  
Jin Liu
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Active Transport ◽  
Conformational Changes ◽  
Molecular Mechanisms ◽  
Sugar Transport ◽  
Potential Of Mean Force ◽  
Coarse Grained ◽  
Lactose Permease ◽  
Protein Conformational Changes

Sugar (one of the critical nutrition elements for all life forms) transport across the cell membranes play essential roles in a wide range of living organism. One of the most important active transport (against the sugar concentration) mechanisms is facilitated by the transmembrane transporter proteins, such as the Escherichia coli lactose permease (LacY) proteins. Active transport of sugar molecules with LacY proteins requires a proton gradient and a sequence of complicated protein conformational changes. However, the exact molecular mechanisms and the protein structural information involved in the transport process are largely unknown. All atom atomistic simulations are able to provide full details but are limited to relative small length and time scales due to the computational cost. The protein conformational changes during sugar transport across LacY are large scale structural reorganization and inaccessible to all atom simulations. In this work, we investigate the molecular mechanisms and conformational changes during sugar transport using coarse-grained molecular dynamics (CGMD) simulations. In our coarse-grained force field, we follow the procedures developed by Han et al. [1, 2], in which the protein model is united-atom based and each heavy atom together with the attached hydrogen atoms is represented by one site, then the protein force filed is coupled with the MARTINI [3] water and lipid force fields. This hybrid force field takes the advantage of the efficiency of MARTINI force field for the environment (water and lipid), while retaining the detailed conformational information for the proteins. Specifically, we develop the new force fields for interactions between sugar molecules and protein by matching the potential of mean force between all-atom and coarse-grained models. Then we validate our force field by comparing the potential of mean force for a glucose interaction with a carbohydrate binding protein from our new force field, with the results from all atom simulations. After validation, we implement the force field for sugar transport across LacY proteins. Through our simulations we are able to capture the formation/breakage of the important hydrogen bonds and salt bridges, which are crucial to the overall conformational changes of LacY.

scholarly journals Coarse-grained simulations of conformational changes in the multidrug efflux transporter AcrB

2017 ◽  
Vol 13 (10) ◽  
pp. 2006-2014 ◽  
Author(s):  
Yead Jewel ◽  
Jin Liu ◽  
Prashanta Dutta
Keyword(s):  
Conformational Changes ◽  
Transmembrane Domain ◽  
Coarse Grained ◽  
Efflux Transporter ◽  
Multidrug Efflux ◽  
Coarse Grained Simulations

Deprotonation of Asp408 in the transmembrane domain induces opening of the cleft and closing of the exit in the porter domain.

Grand-Reaction Method for Simulations of Ionization Equilibria and Ion Partitioning in a Broad Range of pH and Ionic Strength

2019 ◽  
Author(s):  
Jonas Landsgesell ◽  
Oleg Rud ◽  
Pascal Hebbeker ◽  
Raju Lunkad ◽  
Peter Košovan ◽  
...  
Keyword(s):  
Mean Field ◽  
Coarse Grained ◽  
Reactive System ◽  
Acid Base ◽  
Buffer Solution ◽  
Reaction Method ◽  
Ionization Equilibria ◽  
Coarse Grained Simulations ◽  
Ph Range ◽  
Weak Polyelectrolytes

We introduce the grand-reaction method for coarse-grained simulations of acid-base equilibria in a system coupled to a reservoir at a given pH and concentration of added salt. It can be viewed as an extension of the constant-pH method and the reaction ensemble, combining explicit simulations of reactions within the system, and grand-canonical exchange of particles with the reservoir. Unlike the previously introduced methods, the grand-reaction method is applicable to acid-base equilibria in the whole pH range because it avoids known artifacts. However, the method is more general, and can be used for simulations of any reactive system coupled to a reservoir of a known composition. To demonstrate the advantages of the grand-reaction method, we simulated a model system: A solution of weak polyelectrolytes in equilibrium with a buffer solution. By carefully accounting for the exchange of all constituents, the method ensures that all chemical potentials are equal in the system and in the multi-component reservoir. Thus, the grand-reaction method is able to predict non-monotonic swelling of weak polyelectrolytes as a function of pH, that has been known from mean-field predictions and from experiments but has never been observed in coarse-grained simulations. Finally, we outline possible extensions and further generalizations of the method, and provide a set of guidelines to enable safe usage of the method by a broad community of users.<br><br>

scholarly journals Ligand-Induced conformational changes in the lactose permease ofescherichia coli: Evidence for two binding sites

1994 ◽  
Vol 3 (12) ◽  
pp. 2294-2301 ◽  
Author(s):  
Jianhua Wu ◽  
Stathis Frillingos ◽  
John Voss ◽  
H. Ronald Kaback
Keyword(s):  
Conformational Changes ◽  
Binding Sites ◽  
Ofescherichia Coli ◽  
Lactose Permease
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